Elevated mouse hepatic betatrophin expression does not increase human β-cell replication in the transplant setting

Diabetes. 2014 Apr;63(4):1283-8. doi: 10.2337/db13-1435. Epub 2013 Dec 18.

Abstract

The recent discovery of betatrophin, a protein secreted by the liver and white adipose tissue in conditions of insulin resistance and shown to dramatically stimulate replication of mouse insulin-producing β-cells, has raised high hopes for the rapid development of a novel therapeutic approach for the treatment of diabetes. At present, however, the effects of betatrophin on human β-cells are not known. Here we use administration of the insulin receptor antagonist S961, shown to increase betatrophin gene expression and stimulate β-cell replication in mice, to test its effect on human β-cells. Although mouse β-cells, in their normal location in the pancreas or when transplanted under the kidney capsule, respond with a dramatic increase in β-cell DNA replication, human β-cells are completely unresponsive. These results put into question whether betatrophin can be developed as a therapeutic approach for treating human diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Angiopoietin-like Proteins
  • Animals
  • Cell Proliferation / drug effects*
  • Child, Preschool
  • Female
  • Humans
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology*
  • Islets of Langerhans Transplantation
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Peptide Hormones / biosynthesis*
  • Peptides / pharmacology
  • Receptor, Insulin / antagonists & inhibitors
  • Transplantation, Heterologous

Substances

  • ANGPTL8 protein, mouse
  • Angiopoietin-like Proteins
  • Peptide Hormones
  • Peptides
  • S961 peptide
  • Receptor, Insulin